CXCR5, a G-protein coupled receptor, binds to its ligand CXCL13, building a crucial signaling network. This interaction is involved in lymphoid neogenesis, lymphoid organization, and immune responses [1,2]. The CXCL13/CXCR5 axis also contributes to the pathogenesis of several autoimmune diseases, inflammatory diseases, and cancers [1-3].

In a mouse model of sepsis-associated encephalopathy, knocking out CXCR5 enhanced autophagy and partially reversed cognitive deficits, suggesting that CXCR5 may act via the p38MAPK/NF-κB/STAT3 signaling pathway to inhibit hippocampal autophagy during sepsis, contributing to cognitive dysfunction [4]. In the spinal nerve ligation (SNL) model of neuropathic pain, CXCR5 expression induced by SNL was required for SNL-induced activation of spinal astrocytes and microglia, and neuropathic pain was abrogated in Cxcr5-/-mice, indicating CXCR5's role in neuropathic pain [3].

In conclusion, CXCR5 is essential in multiple biological processes and disease conditions. Gene knockout mouse models have revealed its role in cognitive dysfunction in sepsis-associated encephalopathy and neuropathic pain. These findings contribute to understanding the underlying mechanisms of these diseases and may provide potential therapeutic targets related to CXCR5 [3,4].

References:

1. Pan, Zijian, Zhu, Tong, Liu, Yanjun, Zhang, Nannan. 2022. Role of the CXCL13/CXCR5 Axis in Autoimmune Diseases. In Frontiers in immunology, 13, 850998. doi:10.3389/fimmu.2022.850998. https://pubmed.ncbi.nlm.nih.gov/35309354/

2. Wang, Binhan, Wang, Manni, Ao, Danyi, Wei, Xiawei. 2022. CXCL13-CXCR5 axis: Regulation in inflammatory diseases and cancer. In Biochimica et biophysica acta. Reviews on cancer, 1877, 188799. doi:10.1016/j.bbcan.2022.188799. https://pubmed.ncbi.nlm.nih.gov/36103908/

3. Jiang, Bao-Chun, Cao, De-Li, Zhang, Xin, Ji, Ru-Rong, Gao, Yong-Jing. 2016. CXCL13 drives spinal astrocyte activation and neuropathic pain via CXCR5. In The Journal of clinical investigation, 126, 745-61. doi:10.1172/JCI81950. https://pubmed.ncbi.nlm.nih.gov/26752644/

4. Shen, Yanan, Zhang, Yuan, Du, Jiayue, Bao, Hongguang, Si, Yanna. 2021. CXCR5 down-regulation alleviates cognitive dysfunction in a mouse model of sepsis-associated encephalopathy: potential role of microglial autophagy and the p38MAPK/NF-κB/STAT3 signaling pathway. In Journal of neuroinflammation, 18, 246. doi:10.1186/s12974-021-02300-1. https://pubmed.ncbi.nlm.nih.gov/34711216/